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Background: Methadone maintenance treatment (MMT) is an effective treatment for opioid use disorder. However, subtherapeutic dosing may lead to continued opioid use by failing to suppress opioid withdrawal and craving. Preclinical and pilot experimental research suggests that cannabinoids may reduce opioid withdrawal and craving. We sought to test whether the association between low methadone dose and illicit opioid use differs according to concurrent cannabis use patterns. Methods: Data for this study were derived from two community-recruited cohorts of people (≥18 years old) who use illicit drugs in Vancouver, Canada. We used generalized estimating equations to estimate the adjusted association between lower daily MMT dose (

Opioid agonist treatment (OAT) has been shown to improve certain HIV-related treatment measures among people with HIV (PHIV) with opioid use disorder (OUD). However, there is limited data on the impacts of OAT along the whole HIV cascade of care.Using data from an ongoing cohort of PHIV who use drugs in Vancouver, Canada, we used cumulative link mixed-effects models to estimate the independent effect of OAT on achieving progressive steps in the HIV cascade among participants using unregulated opioids daily, after adjusting for confounders.Between 2005 and 2017, we recruited 639 PHIV regularly using opioids (median age 42 years, 59% male, 56% White), of whom 70% were on OAT at their baseline visit. Engagement in OAT showed a nonsignificant trend with higher linkage to HIV care (adjusted partial proportional odds ratio [APPO] = 1.75, 95% confidence interval [CI]: 0.83-3.69), and significantly higher cumulative odds of successfully achieving subsequent HIV cascade steps: on ART (APPO = 3.85, 95% CI: 2.33-6.37); adherent to ART (APPO = 3.15, 95% CI: 2.15-4.62); and HIV viral suppression (APPO = 2.18, 95% CI: 1.51-3.14).This study found a high level of OAT engagement among PHIV using unregulated opioids and that OAT engagement resulted in significantly increased progression through some of the higher steps of the HIV cascade. While these findings are encouraging, they highlight the need to reach populations off OAT to maximize the clinical and community-level benefits of ART.

Owing to advances in antiretroviral therapy (ART), we re-examined minimum ART adherence levels necessary to achieve sustained HIV-1 viral load (VL) suppression among people with HIV who use drugs (PHIV-PWUD).We used data from ACCESS, a community-recruited prospective cohort of PHIV-PWUD in Vancouver, Canada. We calculated adherence using the proportion of days of ART dispensed in the year before each VL measurement. We used generalized linear mixed-effects models to identify adherence- and ART regimen-related correlates of VL suppression (200 copies/ml). We employed probit regression models and generated dose-response curves to estimate the minimum adherence level needed to produce VL suppression in 90% of measures, stratified by regimen and calendar-year.Among 837 ART-exposed PHIV-PWUD recruited between 1996 and 2017, the overall estimated adherence level necessary to achieve 90% VL suppression was 93% (95% confidence interval [CI]: 90-96). This differed by regimen: 69% (95% CI: 45-92) for integrase inhibitor (INSTI)-, 96% (95% CI: 92-100) for boosted protease inhibitor (bPI)-, and 98% (95% CI: 91-100) for non-nucleoside reverse transcriptase inhibitor-based regimens. In multivariable analysis, INSTI-based regimens were positively associated with VL suppression (vs. bPIs), while un-boosted PIs and other regimens were negatively associated. We observed a decreasing temporal trend of estimated adherence necessary for 90% VL suppression, dropping to 64% (95% CI: 50-77) during 2016-2017.Although high levels of ART adherence were necessary to achieve consistent VL suppression, the minimum necessary adherence levels decreased over time. Overall, INSTI-based regimens performed the best, suggesting that they should be preferentially prescribed to PHIV-PWUD.

Objectives: Lower daily methadone dose is negatively associated with retention in methadone maintenance treatment (MMT). Cannabis use during MMT is common, with many patients reporting its use for opioid withdrawal mitigation. We sought to test whether the association between lower MMT dose and treatment retention differs by concurrent high-frequency cannabis use in a community sample of people on MMT. Methods: We obtained data from participants initiating MMT in two community-recruited prospective cohorts of people who use drugs in Vancouver, Canada. We built multivariable Cox frailty models to estimate the relationships between MMT dose (0.05). Structural factors including homelessness and incarceration were significantly and positively associated with treatment discontinuation. Conclusions: Although we previously found the magnitude and strength of the relationship between lower MMT dose and high-frequency unregulated opioid use to be tempered during high frequency cannabis use periods, this effect measure modification does not appear to translate to time retained in treatment. Cannabis-based interventions to promote retention in MMT are unlikely to produce long-term benefit without addressing external factors that place MMT patients at increased risk of treatment discontinuation.

Background The COVID-19 pandemic and consequent public health response may have undermined key responses to the protracted drug poisoning crisis, including reduced access to opioid agonist therapy (OAT) among people with opioid use disorder. Our study objectives were to estimate the prevalence of and identify factors associated with inability to contact OAT prescribers when in need among people on OAT in a Canadian setting during the dual public health crises. Methods Survey data were collected from three prospective cohort studies of community-recruited people who use drugs between July and November 2020, in Vancouver, Canada. A multivariable logistic regression analysis was used to identify potential factors associated with inability to contact OAT prescribers among patients who accessed OAT in the past 6 months. Results Among 448 respondents who reported accessing OAT in the past 6 months, including 231 (54.9%) men, 85 (19.0%) reported having been unable to contact OAT prescribers when needed, whereas 268 (59.8%) reported being able to talk to their prescriber when needed, and 95 (21.2%) reported that they did not want to talk to their medication prescriber in the previous 6 months. Among those who reported inability to contact prescribers, 45 (53.6%) reported that their overall ability to contact prescribers decreased since the start of the pandemic. In multivariable analyses, factors independently associated with inability to talk to OAT prescribers included: chronic pain (Adjusted Odds Ratio [AOR] = 1.82; 95% Confidence Interval [CI] 1.02, 3.27), moderate to severe symptoms of depression or anxiety (AOR = 4.74; 95% CI 2.30, 9.76), inability to access health/social services (AOR = 2.66; 95% CI 1.41, 5.02), and inability to self-isolate or socially distance most or all of the time (AOR = 2.13; 95% CI 1.10, 4.14). Conclusions Overall, approximately one fifth of the sample reported inability to contact their OAT prescribers when needed, and those people were more likely to have co-occurring vulnerabilities (i.e., co-morbidities, inability to access health/social services) and higher vulnerability to COVID-19. Interventions are needed to ensure optimal access to OAT and mitigate the deepening health inequities resulting from the COVID-19 pandemic and the escalating drug poisoning crisis.

Introduction and aims North America is currently experiencing an epidemic of opioid overdose deaths, driven by the proliferation of fentanyl in the street drug market. Although buprenorphine/naloxone (BUP/NX) is an evidence-based, first-line opioid agonist for the management of opioid use disorder, a key challenge in its prescribing lies in the fact that it can precipitate opioid withdrawal during its initial induction process. At this time, there is minimal literature on the BUP/NX induction process in individuals who use illicit fentanyl regularly. Design, methods and results A case series from a Vancouver, Canada addiction medicine clinic of three fentanyl-exposed patients who experienced unexpected, precipitated withdrawal when initiating BUP/NX. Discussion and conclusion These cases describe incidents of precipitated opioid withdrawal occurring after unusually long periods of fentanyl abstention. Although fentanyl is experienced as a short-acting opioid, the drug persists much longer in the body's peripheral tissues. Here, we highlight the new challenges fentanyl may pose to current BUP/NX induction strategies, and explore the possibility of a long-acting pharmacokinetic effect of fentanyl in the setting of repeated illicit use.

People living with HIV (PLWH) often experience stigma and discrimination by health care professionals. We investigated the prevalence of perceived mistreatment in health care settings and its associations with HIV clinical outcomes and health care-seeking behaviour using data from a long-running prospective cohort of PLWH who use drugs. Of the 857 participants included, 19% reported at least one instance of perceived mistreatment during the study period. In adjusted longitudinal analyses, perceived mistreatment was positively associated with not being on ART in the same follow-up period, and participants who reported perceived mistreatment were less likely to report seeing a physician in the subsequent follow-up period. Daily use of injection drugs was positively associated with reporting perceived mistreatment. These findings demonstrate the implications of negative health care interactions in a population that must consistently engage with the health care system, and the need for stigma-reducing educational interventions for health care professionals.

Introduction and Aims: Illicitly-manufactured fentanyl continues to fuel the opioidoverdose crisis throughout the United States and Canada. However, little is known about factors associated with knowingly or unknowingly using fentanyl. Therefore, we sought to identify the prevalence and correlates of suspected/known and unknown exposure to fentanyl (excluding the prescribed one) among people who inject drugs (PWID), including associated overdose risks. Design and Methods: Data were derived from three prospective cohort studies of community-recruited people who use drugs in Vancouver, Canada in 2016–2017. Multivariable logistic regression was used to identify correlates of suspected/known exposure (i.e., urine drug screen positive [UDS+] and self-reporting past three-day exposure) and unknown exposure to fentanyl (i.e., UDS+ and self-reporting no past three day exposure), respectively. Results: Among 590 PWID, 296 (50.2%) tested positive for fentanyl. Of those, 143 (48.3%) had suspected/known and 153 (51.7%) had unknown exposure to fentanyl. In multivariable analyses, using supervised injection sites and possessing naloxone were associated with both suspected/known and unknown exposure (all p

BACKGROUND AND AIMS: To improve evidence-based addiction care in acute care settings, many hospitals across North America are developing an inpatient addiction medicine consultation service (AMCS). St Paul’s Hospital in Vancouver, Canada houses a large interdisciplinary AMCS. This study aimed to: (1) describe the current model of clinical care and its evolution over time; (2) evaluate requests for an AMCS consultation over time; (3) highlight the established clinical training opportunities and educational curriculum and (4) provide some lessons learned. DESIGN, SETTING AND PARTICIPANTS: A retrospective observational analysis in an urban, academic hospital in Vancouver, Canada with a large interdisciplinary AMCS, studied from 2013 to 2018, among individuals who presented to hospital and had a substance use disorder. MEASUREMENTS: Data were collected using the hospital’s electronic medical records. The primary outcome was number of AMCS consultations over time. FINDINGS: In 2014 the hospital’s AMCS was restructured into an academic, interdisciplinary consultation service. A 228% increase in the number of consultations was observed between 2013 (1 year prior to restructuring) and 2018 (1373 versus 4507, respectively; P = 0.027). More than half of AMCS consultations originated from the emergency department, with this number increasing over time (55% in 2013 versus 74% in 2018). Referred patients were predominantly male (> 60% in all 5 years) between the ages of 45 and 65 years. Reasons for consultation remained consistent and included: opioids (33%), stimulants (30%), alcohol (23%) and cannabis use (8%). CONCLUSIONS: After St Paul’s Hospital in Vancouver, Canada was restructured in 2014 to a large, interdisciplinary addiction medicine consultation service (AMCS), the AMCS saw a 228% increase in the number of consultation requests with more than half of requests originating from the emergency department. Approximately two-thirds of consultation requests were for opioid or stimulant use.

BACKGROUND: With the emergence of illicitly-manufactured fentanyl, drug overdose deaths have risen in unprecedented numbers. In this context, there is an urgent need to characterize potential changes in drug use behaviors among people who use drugs (PWUD). OBJECTIVE: To examine changes in drug use behaviors following the emergence of illicit fentanyl among people who use drugs (PWUD). METHODS: Data for this cross-sectional analysis was derived from three prospective cohorts of PWUD between December 2016 and May 2017 in Vancouver, Canada. Multivariable logistic regression was used to determine factors associated with self-reported behavior changes (binary variable “yes” or “no”) following the emergence of illicit fentanyl. RESULTS: Among 999 participants [363 (36.3%) females], 388 (38.8%) reported some behavior change. The remaining 611 (61.2%) reported no change in behavior; 240 (39.3%) of these individuals had recently been exposed to fentanyl. In multivariable analyses, factors independently associated with behavior change included recent non-fatal overdose (Adjusted Odds Ratio [AOR] = 2.28), active injection drug use (AOR = 1.96), being on opioid agonist therapy (AOR = 1.80), and urine drug screen positive for fentanyl (AOR = 1.45), (all p< .05). CONCLUSION: The majority of PWUD in our sample did not change their drug use behavior despite a high prevalence of fentanyl exposure, indicating a need for targeted behavior change messaging and overdose prevention efforts such as naloxone and addiction treatment for this sub-population of PWUD. Further, the high fentanyl exposure observed in our sample suggests a need to address upstream structural factors shaping the overdose risk in addition to individual behavioral change.

Introduction and aims Buprenorphine/naloxone is an evidence-based treatment for opioid use disorder, but an identified limitation is the period of required opioid abstinence prior to induction on the medication. 'Micro-dosing', or using incrementally increasing doses of buprenorphine/naloxone over time, may be a way to overcome this challenge as it can be done in parallel with the ongoing use of other opioids (either illicit or prescribed). Design and methods A retrospective case series (January to December 2018) was completed of seven participants who underwent buprenorphine/naloxone induction using micro-dosing at two outpatient addiction clinics in Vancouver, Canada. Results Seven participants completed a 7-day buprenorphine/naloxone micro-dosing protocol. Prior to and during the induction, one participant was prescribed methadone, three were prescribed slow release oral morphine and three used only illicit fentanyl. Participants were prescribed sublingual buprenorphine/naloxone: 0.5 mg once daily (day 1), 0.5 mg twice daily (BID; day 2), 1 mg BID (day 3), 2 mg BID (day 4), 3 mg BID (day 5), 4 mg BID (day 6) and 12 mg once daily (day 7). On day 7, all prescribed or illicit full opioid agonists were discontinued. Buprenorphine/naloxone was subsequently titrated to a daily dose of between 12 and 32 mg. All patients reported success with buprenorphine/naloxone induction with no precipitated withdrawal. Discussion and conclusions Buprenorphine/naloxone micro-dosing may offer a promising alternative approach for successful induction for individuals with opioid use disorder who desire treatment with buprenorphine/naloxone, and further research to determine effectiveness is warranted.

BACKGROUND: People who use injection drugs (PWID) experience high rates of HIV acquisition and, as a result of lower rates of optimal access and adherence to combination antiretroviral therapy (ART), experience worse HIV treatment outcomes compared to other key affected populations. However, the incidence and risk factors for the development of AIDS among HIV-positive PWID have not been completely described. METHODS: We used data from a community-recruited prospective cohort of HIV-positive PWID in Vancouver, Canada, a setting with universal no-cost ART and a comprehensive clinical monitoring registry. We used multivariable extended Cox models to identify factors associated with time to AIDS. RESULTS: Between 1996 and 2017, 396 participants, including 140 (35.4%) women, were followed for a median of 39.0 months (interquartile range: 16.6 - 76.2), among whom 165 (41.7%) developed AIDS. In a multivariable model, homelessness (Adjusted Hazard Ratio [AHR] = 1.76 (1.18-2.61) and injection drug use within the preceding six months (AHR = 1.74 (1.17-2.58) were independently associated with higher risk of developing AIDS. CONCLUSIONS: Despite widespread scale-up of programs to improve ART utilization, significant risk factors for development of AIDS remain among HIV-positive PWID in this setting.

Background: Prior evidence suggests that plasma HIV viral load is elevated during periods of crack cocaine use independent of antiretroviral therapy (ART) exposure. We sought to evaluate the effect of crack cocaine use frequency on HIV disease severity among HIV-positive people who use unregulated drugs (PWUD). Methods: We analyzed data from the ACCESS study, an open prospective cohort of HIV-positive PWUD including comprehensive HIV clinical monitoring in a setting with no-cost healthcare, including ART. Multivariable generalized linear mixed-effects models were used to estimate the independent effect of time-updated crack cocaine use frequency on HIV disease severity, adjusting for ART exposure and relevant confounders. HIV disease severity was measured using the Veterans Aging Cohort Study (VACS) Index, which is a validated prognostic index. Findings: Between 2005 and 2018, 806 individuals were recruited and contributed 8,537 observations. At baseline, the frequencies of crack cocaine use in the previous 180 days were: none (187, 23%), less than weekly (150, 19%), weekly (229, 28%), and daily or greater (240, 30%). In multivariable models adjusted for ART exposure and other confounders, daily or greater frequency of crack cocaine use was significantly associated with higher VACS Index scores (β = 0.9, 95% confidence interval: 0.2, 1.6) as compared to none. Interpretation: Daily or greater frequency of crack cocaine use may exacerbate HIV disease severity among HIV-positive PWUD. Although the observed effect was small, it was also independent of ART exposure. As this finding has been supported by previous evidence, the observed difference may reflect an underlying biological mechanism or other factors linked with crack cocaine use although further investigation is warranted. Funding Information: US National Institutes of Health. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The ACCESS study was approved by the University of British Columbia/Providence Healthcare Research Ethics Board.

BACKGROUND: To evaluate how an international one-year intensive research training program for addiction medicine physicians contributed to subsequent research involvement and productivity. METHODS: We prospectively compared addiction medicine physician fellows admitted to a one-year training program with non-admitted controls, using baseline questionnaire and peer-reviewed publication data. Participants’ publication activity was assessed from fellowship application date onwards using biomedical databases (e.g., PubMed, Embase). RESULTS: Between July 2014 and June 2020, which is six years of cohorts, 56 (39 women) physicians, both fellows (n = 25) and non-admitted applicants (n = 31), were observed and included in the study, contributing 261 person-years of observation. At baseline, in the fellows’ cohort: 76% of participants (19/25) reported past research involvement, 24% (6/25) had one or more advanced graduate degrees (e.g., MPH), and the median number of peer-reviewed, first author publications was one (Interquartile Range [IQR] = 0–2). At baseline, in the controls’ cohort: 84% of participants (26/31) reported past research involvement, 39% (12/31) had one or more advanced graduate degrees, and the median number of peer-reviewed, first author publications was zero. The physicians’ training included internal medicine (n = 8), family medicine (n = 33), psychiatry (n = 5) and others (n = 4). At follow up, there was a significant difference between fellows (n = 25) and controls (n = 31) in total number of publications (Rate Ratio [RR] = 13.09, 95% Confidence Interval [CI], 5.01 − 34.21, p < 0.001), as well as first author publications (RR = 5.59, 95% CI, 2.23 − 14.06, p < 0.001). CONCLUSION: In the six-year observation period, fellows’ productivity indicates undertaking this fellowship was associated with significant research outputs in comparison to controls, signaling successful training of addiction physicians to help recruit addiction medicine physicians to participate in addiction research.

OBJECTIVES Gaps in addiction medicine training are a reason for poor substance use care in North America. Hospital addiction medicine consult services (AMCS) provide critical medical services, including screening and treatment of substance use disorders. Although these programs often feature an educational component for medical learners, the impact of AMCS teaching on objective knowledge and career aspirations in addiction medicine has not been well described. METHODS The authors report findings from two sequential studies conducted at a large academic hospital in Vancouver, Canada. The first study assessed the impact of an AMCS clinical rotation on medical trainee addiction medicine objective knowledge using an online survey of 6 true/false questions before and after the rotation. The second study examined the impact of an AMCS rotation on career aspirations using 4 seven-point Likert-type questions. One-sample t tests on mean differences (MD) with Benjamini-Hochberg adjustment for multiple comparisons were employed for statistical analyses. RESULTS Between May 2017 and June 2018, knowledge scores were significantly higher postrotation (MD = 4.78, standard deviation [SD] = 19.5, P = 0.034) among 115 medical trainees. Between July 2018 and July 2019, aspirations to practice addiction medicine were significantly more favorable postrotation (MD = 3.48, SD = 3.15, P

We sought to evaluate the impact of homelessness on HIV disease progression among people who use unregulated drugs (PWUD) living with HIV and test if this association was mediated by adherence to antiretroviral therapy (ART). We applied general linear mixed-effects modeling to estimate the longitudinal relationship between homelessness and the Veterans Aging Cohort Study (VACS) Index, a validated measure of HIV disease progression that predicts all-cause mortality, among a prospective cohort of PWUD. In a longitudinal model adjusted for ART adherence, homelessness was significantly associated with increased VACS Index scores and 16% of the association was mediated by ART adherence. These findings indicate that homelessness was a significant risk factor for HIV disease progression and this association was marginally mediated by ART adherence. Future studies are needed to quantify the other mechanisms (e.g., food insecurity, mental health) by which homelessness increases mortality risk among PWUD living with HIV.

In the context of the ongoing overdose crisis, a stark increase in toxic drug deaths from the unregulated street supply accompanied the onset of the COVID-19 pandemic. Injectable opioid agonist treatment (iOAT - hydromorphone or medical-grade heroin), tablet-based iOAT (TiOAT), and safer supply prescribing are emerging interventions used to address this crisis in Canada. Given rapid clinical guidance and policy change to enable their local adoption, our objectives were to describe the state of these interventions before the pandemic, and to document and explain changes in implementation during the early pandemic response (March-May 2020).Surveys and interviews with healthcare providers comprised this mixed methods national environmental scan of iOAT, TiOAT, and safer supply across Canada at two time points. Quantitative data were summarized using descriptive statistics; interview data were coded and analyzed thematically.103 sites in 6 Canadian provinces included 19 iOAT, 3 TiOAT and 21 safer supply sites on March 1, 2020; 60 new safer supply sites by May 1 represented a 285% increase. Most common substances were opioids, available at all sites; most common settings were addiction treatment programs and primary care clinics, and onsite pharmacies models. 79% of safer supply services were unfunded. Diversity in service delivery models demonstrated broad adaptability. Qualitative data reinforced the COVID-19 pandemic as the driving force behind scale-up.Data confirmed the capacity for rapid scale-up of flexible, community-based safer supply prescribing during dual public health emergencies. Geographical, client demographic, and funding gaps highlight the need to target barriers to implementation, service delivery and sustainability.

OBJECTIVES: Methamphetamine use is rising globally and we have limited treatments for this. Subgroups within the diverse methamphetamine-using population may have distinct treatment needs. Among a community-recruited sample of people who use crystal methamphetamine, we aimed to identify subgroups and characterize their overdose risk and access to addiction care. METHODS: Data from prospective cohorts of people who use drugs in Vancouver, Canada from 2014 to 2018 were used to conduct a repeated measures latent class analysis among participants who used crystal methamphetamine. Multivariable generalized estimating equations models were fit to determine the associated factors. RESULTS: Among 824 eligible participants, a five-class model was identified as the best fit: (1) primary stimulant use (15.7%); (2) women engaged in sex work and opioid use (21.4%); (3) street income generation and opioid use (31.6%); (4) opioid agonist therapy (OAT) patients (22.3%); and (5) men who have sex with men (9.0%). In multivariable analyses, compared to the primary stimulant use group, non-fatal overdose was positively associated with street income generation (adjusted odds ratio [AOR] = 1.49, 95% confidence interval [95% CI]=1.30–1.71), sex work (AOR = 1.38, 95% CI=1.20–1.59) and OAT (AOR = 1.22, 95% CI=1.06–1.41) subgroups; engagement in non-OAT addiction care was negatively associated with street income generation (AOR = 0.81, 95% CI=0.68–0.97) and sex work (AOR = 0.78, 95% CI=0.63–0.98) subgroups. DISCUSSION: Socioeconomically marginalized subgroups with opioid and crystal methamphetamine co-use were at highest risk of non-fatal overdose and had poorer access to addiction care, highlighting the need for tailored interventions.

Canada and the United States (U.S.) face an epidemic of opioid use disorder (OUD) and opioid overdose. The most effective OUD treatment is opioid agonist therapy (OAT)—buprenorphine (with and without naloxone) and methadone. Although federal approval for OAT occurred decades ago, in both countries, access to and use of OAT is low. Restrictive policies and complex regulations contribute to limited OAT access. Through a non-systematic literature scan and a review of publicly available policy documents, we examined and compared OAT policies and practice at the federal (Canada vs. U.S.) and local levels (British Columbia [B.C.] vs. Oregon). Differences and similarities were noted between federal and local OAT policies, and subsequently OAT access. In Canada, OAT policy control has recently shifted from federal to provincial authorities. Conversely, in the U.S., federal authorities maintain primary control of OAT regulation. Local OAT health insurance coverage policies were substantively different between B.C. and Oregon. In B.C., five OAT options were available, while in Oregon, only two OAT options were available with administrative limitations. The differences in local OAT access and coverage policies between B.C. and Oregon, may be explained, in part, to the differences in Canadian and U.S. federal OAT policies, specifically, the relaxation of special federal OAT regulatory controls in Canada. The analysis also highlights the complicating contributions, and likely policy solutions, that exist within other drug policy sub-domains (e.g., the prescription regime, and drug control regime) and broader policy domains (e.g., constitutional rights). U.S. policymakers and health officials should consider adopting Canada’s regulatory policy interventions to expand OAT access to mitigate the harms of the ongoing opioid overdose epidemic.

KEY POINTS In 2018, at least 4460 Canadians died from an opioid overdose, of which 94% were determined to be unintentional (accidental) overdoses. This represents a 9% increase in overdose deaths from 2017 and a 48% increase from 2016.[1][1] The recent emergence of street fentanyl, carfentanil and

Among HIV-positive people who use illicit drugs (PWUD) in our setting, repeated periods of incarceration adversely affect ART adherence in a dose-dependent manner. However, the impact of non-custodial criminal justice involvement on HIV-related outcomes has not been previously investigated. Data were obtained from a longitudinal cohort of HIV-positive PWUD in a setting of universal no-cost ART and complete dispensation records. Multivariate generalized estimating equations were used to calculate the longitudinal odds of having a detectable HIV VL (VL) associated with custodial and non-custodial CJS exposure. Between 2005 and 2014, 716 HIV-positive ART-exposed PWUD were recruited. In multivariate analysis, both custodial [Adjusted odds ratio (AOR) 0.61, 95% CI 0.45–0.82] and noncustodial (AOR 0.78, 95% CI 0.62–0.99) involvement in the criminal justice system was associated with detectable HIV VL. Among HIV-positive PWUD, both custodial and non-custodial criminal justice involvement is associated with worse HIV treatment outcomes. Our findings highlight the need for increased ART adherence support across the full spectrum of the criminal justice system.

Background:Co-prescribing benzodiazepines and opioids is relatively contraindicated due to the possible overdose risk. However, people living with HIV (PLWH) may have concurrent psychiatric and/or chronic pain diagnoses that may lead to the use of opioids and/or benzodiazepines for symptomatic treatment. Consequently, some PLWH may be at-risk for the health harms associated with the co-prescribing of these medications. Given this, the objectives of this study were to first examine the prevalence of opioids and benzodiazepines co-prescribing, and second, to characterize patient factors associated with the co-prescribing of opioids and benzodiazepines among PLWH in British Columbia (BC), Canada. Methods:Using data derived from a longitudinal BC cohort, we used bivariable and multivariable generalized estimating equation models to establish the prevalence of a benzodiazepine and opioid co-prescription and determine factors associated with this practice. Results:Between 1996 and 2015, 14 484 PLWH were included in the study and were followed for the entire study period. At baseline, 548 people (4%) were co-prescribed opioids and benzodiazepines, 6593 (46%) were prescribed opioids only, 2887 (20%) were prescribed benzodiazepines only, and 4456 (31%) were prescribed neither medication. A total of 3835 (27%) participants were prescribed both medications at least once during the study period. Factors positively associated with concurrent opioid and benzodiazepine prescribing included: depression/mood disorder [adjusted odds ratio (AOR) = 1.32; 95% confidence interval (CI) = 1.22–1.43] and anxiety disorder (AOR = 1.45; 95% CI = 1.27–1.66), whereas female sex (AOR = 0.76; 95% CI = 0.64-0.91) and substance use disorder (SUD) (AOR = 0.82; 95% CI = 0.74–0.90) were negatively associated with the outcome. Conclusion:Our findings indicate that co-prescription of opioids and benzodiazepines was seen at some point during study follow-up in over a quarter of PLWH. Given the known risks associated with this prescribing practice, future research can focus on the outcomes of co-prescribing among this patient population and the development of strategies to reduce the co-prescribing of opioids and benzodiazepines.

North America is in the midst of an overdose crisis, with up to 130 Americans dying daily from a preventable drug overdose. Opioids account for 70% of overdose deaths. Despite government efforts to improve access to opioid use disorder (OUD) treatment and the implementation of various harm reduction initiatives, overdose mortality remains unacceptably high. Although effective treatments exist for OUD (eg, opioid agonist therapies like buprenorphine/naloxone and methadone), many individuals do not achieve stabilization with these medications. Tablet injectable opioid agonist therapy (TiOAT) is an initiative being piloted in British Columbia to provide witnessed access to a safer opioid supply for individuals with treatment-refractory OUD. The program offers participants a safer opioid supply through physician-prescribed pharmaceutical-grade hydromorphone tablets. TiOAT is suitable for individuals with severe OUD who are actively injecting opioids and are refractory to conventional OUD treatment. As such, a scale-up of the TiOAT program may be a feasible alternative to address persistent opioid-related deaths in North America, while minimizing potential harms associated with unwitnessed safer supply opioid prescribing (eg, diversion and overdose). Although a comprehensive evaluation of TiOAT is of critical importance (including an assessment of the program's adverse events), completion of the evaluation should not preclude scale-up of the program in the interim as a strategy to reduce opioid-related harms.

Background While patient-reported treatment dissatisfaction is considered an important factor in determining the success of substance use disorder treatment, the levels of dissatisfaction with opioid agonist therapies (OAT) and its relationship with the risk of fentanyl exposure have not been characterized in the context of the ongoing opioid overdose crisis in the US and Canada. Our primary hypothesis was that OAT dissatisfaction was associated with an increased odds of fentanyl exposure. Methods Our objective was to examine self-reported treatment satisfaction among OAT patients in Vancouver, Canada and the association with fentanyl exposure. Longitudinal data were derived from 804 participants on OAT enrolled in two community-recruited harmonized prospective cohort studies of people who use drugs in Vancouver between 2016 and 2018 via semi-annual interviews and urine drug screens (UDS). We employed multivariable generalized estimating equations to examine the relationship between OAT dissatisfaction and fentanyl exposure. Results Out of 804 participants (57.0% male), 222 (27.6%) reported being dissatisfied with OAT at baseline and 1070 out of 1930 observations (55.4%) had fentanyl exposure. The distribution of OAT reported in the sample was methadone (n = 692, 77.7%), buprenorphine-naloxone (n = 82, 9.2%), injectable OAT (i.e., diacetylmorphine or hydromorphone; (n = 65, 7.3%), slow-release oral morphine (n = 44, 4.9%) and other/study medication (n = 8, 1.0%). In the multivariable analysis, OAT dissatisfaction was positively associated with fentanyl exposure (AOR = 1.34; 95% CI: 1.08–1.66). Conclusions A substantial proportion of OAT patients in our sample reported dissatisfaction with their OAT, and more than half were exposed to fentanyl. We also found that those who were dissatisfied with their OAT were more likely to be exposed to fentanyl. These findings demonstrate the importance of optimizing OAT satisfaction in the context of the ongoing opioid overdose crisis.

The United States and Canada are experiencing an opioid overdose crisis driven largely by exposure to fentanyl (a potent synthetic opioid), with little known about fentanyl exposure among HIV-positive people who use unregulated drugs (PWUD). We sought to estimate the prevalence and correlates of fentanyl exposure among a community-recruited sample derived from a prospective cohort study of HIV-positive PWUD in Vancouver, Canada. Generalized linear mixed-effects analyses were used to identify longitudinal factors associated with a fentanyl-positive urine drug screen test. Between June 2016-November 2017, 456 participants were recruited and contributed 1007 observations. At baseline, 96% of participants were ART-exposed, 72% had an HIV viral load (VL)

Background Injectable opioid agonist treatment (iOAT) is an emerging evidence-based option in the continuum of care for opioid use disorder in parts of Canada. Our study objective was to identify and describe iOAT programs operating during the ongoing opioid overdose crisis. Methods We conducted 2 sequential environmental scans. Programs were eligible to participate if they were in operation as of Sept. 1, 2018, and Mar. 1, 2019. Information was collected over 2-3 months for each scan (September-October 2018, March-May 2019). Programs that participated in the first scan and newly established programs were invited to participate in the second scan. The scans included questions about location, service delivery model, clinical and operational characteristics, numbers and demographic characteristics of clients, and program barriers and facilitators. Descriptive analysis was performed. Results We identified 14 unique programs across the 2 scans. Eleven programs located in urban centres in British Columbia and Ontario participated in the first scan. At the time of the second scan, 2 of these programs were on hold and 2 of 3 newly established programs were in Alberta. The total capacity of all participating programs was 420 clients at most. Four service delivery models were identified; iOAT was most commonly integrated within existing health and social services. All programs offered hydromorphone, and 1 program also offered diacetylmorphine. In the first scan, 73% of clients (133/183) were male; the mean age of clients was 47 years. Limited capacity, pharmacy operations and lack of diacetylmorphine access were among the most frequently reported barriers. The most commonly reported facilitators included client-centred care, client relationships and access to other health and social support. Interpretation Evidence indicates that iOAT can be successfully implemented using diverse service delivery models. Future work should facilitate scale-up of this evidence-based treatment where gaps persist in high-risk communities.

Background Across North America, there is an unprecedented opioid overdose epidemic. Approximately 15% of individuals with severe opioid use disorder (OUD) do not benefit from opioid agonist therapy (OAT) such as buprenorphine/naloxone or methadone and are considered treatment refractory. Of those who inject, injectable OAT (iOAT), with hydromorphone or diacetylmorphine, offered in community settings has demonstrated improved retention to treatment and decreased nonprescription opioid use. This case series seeks to describe iOAT initiation and titration in a hospital setting for treatment refractory individuals with OUD and examine impacts of iOAT on leaving hospital against medical advice (AMA). Methods A retrospective chart review of 4 patients initiated on iOAT during hospitalization at St. Paul's Hospital in Vancouver, BC was completed between July 2017 to May 2018. Outcomes of interest included: (1) dose titration schedules of hydromorphone; and (2) reports of leaving hospital AMA; and (3) continuation of iOAT in community postdischarge. Results Of the 4 participants, 2 were female and the mean age was 42 years. Despite a history of AMA, all participants stayed until the recommended the discharge after iOAT initiation. The average total doses of intravenous hydromorphone used during titration were: day 1: 100 mg and days 2 to 3: 200 mg. All continued iOAT in the community and one participant was readmitted within 30 days postdischarge. Interpretation This case series describes a novel approach to the management of treatment refractory individuals with severe OUD during hospitalization. Prescribing iOAT in acute care settings is feasible and may reduce rates of leaving hospital AMA.

Background Opioid agonist therapy (OAT) models are generally provided without consideration of how pre-treatment characteristics may be associated with outcome. Therefore, we aimed to first characterize longitudinal trajectories of opioid use before initiating OAT. Then we explored the impact of OAT on opioid use across these pre-treatment trajectories. Methods Data were derived from three prospective cohort studies involving people who use drugs in Vancouver, Canada. Latent class growth analysis was applied to identify opioid use trajectories based on individual-level observations three years before starting OAT. Multivariable generalized linear mixed model was used to examine whether engaging in OAT was associated with lower risk of illicit opioid use among participants with different pre-treatment opioid use trajectories. Results 464 participants were included in the study between September 2005 and November 2018. Two pre-treatment opioid use trajectories were identified: high frequency users (246, 53.0%) and gradually increasing frequency users (218, 47.0%). We observed different strengths of association between OAT engagement and illicit opioid use among high frequency users (adjusted odds ratio [AOR] = 0.36, 95% Confidence Interval [CI]: 0.20 – 0.63) and gradually increasing frequency users (AOR = 0.91, 95% CI: 0.53 – 1.56). Unstable housing, any stimulant use, experiencing violence, drug dealing, sex work involvement, and incarceration were independently and positively associated with ongoing illicit opioid use. Conclusions Distinct pre-treatment opioid use trajectories are likely to influence treatment outcomes. Research is required to determine if tailored strategies specific to people with different pre-treatment opioid use patterns have potential to improve outcomes of OAT.

International audience; Background: Methamphetamine use is common among some populations of gay, bisexual and other men who have sex with men (gbMSM). This study reviewed the status of research on the efficacy of interventions that address harms among gbMSM who use methamphetamine.Methods: We searched MEDLINE, PsycINFO, CINAHL, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Google Scholar to identify publications from inception to October 23, 2017, that assessed an intervention addressing methamphetamine use among gbMSM.Results: Of 1896 potential studies and 935 unique articles screened for inclusion, 28 eligible studies assessed 26 different interventions in the following categories: pharmacological (n = 5); psychosocial (n = 20); harm reduction (n = 1). Given that outcome variables were measured in highly variable ways, we were unable to conduct a meta-analysis of intervention effects. However, 22 studies reported a statistically significant effect on one or more methamphetamine-related outcomes. Among 21 studies that included measures of sexual health-related outcomes, 18 reported a significant effect on one or more sexual health-related outcomes, and 15 of those reported a concurrent effect on both drug- and sexual health-related outcomes.Conclusions: This is the first review to provide compelling evidence that integrating interventions to address both drug- and sexual-related harms for gbMSM who use methamphetamine can be efficacious. Future research should focus on identifying differential effects of various intervention approaches by social positioning, as well as prioritize future evaluations of integrated harm reduction interventions (e.g., the distribution of harm reduction kits within sexual health care settings).

The Veterans Aging Cohort Study (VACS) index combines commonly collected clinical biomarkers to estimate human immunodeficiency virus (HIV) disease severity. Among a prospective cohort of people living with HIV who use illicit drugs (PWUD) (n = 948), we found that the VACS index was significantly associated with mortality over a 20-year study period.

Background Within the context of the ongoing overdose crisis and limitations of conventional opioid treatments, the scale-up of injectable hydromorphone (HDM) and diacetylmorphine (DAM) as evidenced-based treatments is currently underway in some settings in Canada. Past research has underscored the importance of treatment initiation in shaping onward treatment trajectories, however structural factors that influence participants' motivations to access injectable HDM or DAM have not been fully characterized. This study examines peoples’ motivations for accessing HDM/DAM treatment and situates these within the social and structural context that shapes treatment delivery by employing the concept of structural vulnerability. Methods Fifty-two individuals enrolled in injectable HDM/DAM programs were recruited from four community-based clinical programs in Vancouver, Canada to participate in qualitative semi-structured interviews. Approximately 50 h of ethnographic fieldwork was also completed in one clinical setting, and one-on-one with participants public spaces. Interview transcripts and ethnographic fieldnotes were analyzed through a structural vulnerability lens with a focus on treatment initiation. Results Participants’ previous experiences and perceptions of other drug treatments (e.g. methadone) foregrounded their initiation of injectable HDM/DAM. Social and structural factors (e.g. fentanyl-adulterated drug supply, poverty, drug criminalization) influenced participants’ motivations to address immediate physical risks and their initial perception of this treatment's ability to align with their opioid use experiences. Similar social and structural factors that drive immediate physical risks, were also evidenced in participants’ motivations to make changes in their daily lives and to address broader opioid use goals. Conclusion Participants descriptions of their motivations to initiate HDM/DAM highlight how structural vulnerabilities shaped participants’ experiences initiating injectable HDM/DAM.

Background North America is facing an unprecedented public health crisis of opioid-related morbidity and mortality, increasingly as a result of the introduction of illicitly manufactured fentanyl into the street drug market. Although the treatment of opioid use disorder (OUD) is a key element in the response to the opioid overdose epidemic, currently available pharmacotherapies (e.g., methadone, buprenorphine) may not be acceptable to or effective in all patients. Available evidence suggests that slow-release oral morphine (SROM) has similar efficacy rates as methadone with respect to promoting abstinence, and with improvements in a number of patient-reported outcomes among persons using heroin. However, little is known about the relative effectiveness and acceptability of SROM compared to methadone in the context of fentanyl use. This study aims to address this research gap. Methods pRESTO is a 24-week, open-label, two arm, non-inferiority, randomized controlled trial comparing SROM versus methadone for the treatment of OUD. Participants will be 298 clinically stable, non-pregnant adults with OUD, recruited from outpatient clinics in Vancouver, Canada, where the majority of the illicit opioids are contaminated with fentanyl. The primary outcome is suppression of illicit opioid use, measured by bi-weekly urine drug screens. Secondary outcomes include: treatment retention, medication safety, overdose events, treatment satisfaction, psychological functioning, changes in drug-related problems, changes in quality of life, opioid cravings, other substance use, and cost-effectiveness. Discussion pRESTO will be among the first studies to evaluate treatment options for individuals primarily using synthetic street opioids, providing important evidence to guide treatment strategies for this population.